Pet-1, a novel ETS domain factor that can activate neuronal nAchR gene transcription.
We report a cDNA clone prepared from adrenal chromaffin-derived PC12 cell RNA that encodes a novel ETS-domain factor, Pet-1. The deduced primary structure of Pet-1 is composed of 340 amino acids and the encoded polypeptide has a predicted molecular mass of 35.4 kD. The pattern of Pet-1 gene expression in the neonatal rat is highly restricted and suggests that Pet-1 functions primarily in the nervous system. Adrenal gland expresses the highest level of Pet-1 among the tissues examined. In situ hybridization indicates that Pet-1 is expressed in the adrenal medulla but not the adrenal cortex. Slightly weaker Pet-1 hybridization is detected in brain and low levels are detectable in intestine and eye. Pet-1 can bind specifically to a PEA3 ETS DNA-binding motif and can modulate transcription of synthetic promoter constructs in a sequence-specific manner. We recently identified a neural cell-type specific enhancer, beta43', within the 3'-untranslated exon of the neuronal nicotinic acetylcholine receptor (nAchR) beta4 subunit gene. Similar to Pet-1, the beta4 gene is also expressed in PC12 cells. The presence of putative ETS-domain binding sites in the beta43' enhancer led us to hypothesize that members of the ets gene family activate neuronal nAchR genes. Cotransfection assays show that Pet-1 can activate reporter gene transcription in a beta43' enhancer-dependent and cell type-dependent manner. Our results lead us to hypothesize that Pet-1 acts as a transcriptional regulator of downstream target genes involved in cholinergic neurotransmission.
Fyodorov
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Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Nelson
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Deneris
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D005810:Multigene Family; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D016716:PC12 Cells; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000235:genetics*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*
C110759:Fev protein, rat; D011518:Proto-Oncogene Proteins; D011978:Receptors, Nicotinic; D014157:Transcription Factors